Kidney Week

Abstract: TH-PO250

Glomerular Permselectivity Associates With Higher Risk of Kidney Failure and Death in Type 2 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Saulnier, Pierre Jean, National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States

Pierre Jean Saulnier,

• Looker, Helen C., National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States

Helen C. Looker,

• Layton, Anita T., University of Waterloo, Waterloo, Ontario, Canada

Anita T. Layton,

• Lemley, Kevin V., University of Southern California, Los Angeles, California, United States

Kevin V. Lemley,

• Nelson, Robert G., National Institute of Diabetes and Digestive and Kidney Diseases, Chronic Kidney Disease Section, Phoenix, Arizona, United States

Robert G. Nelson,

• Bjornstad, Petter, University of Colorado, Aurora, Colorado, United States

Petter Bjornstad,

Background

Hydrodynamic models of hindered solute transport are used to characterize the size selective properties of the glomerular barrier. One model assumes the glomerular capillary is perforated by restrictive cylindrical pores of identical pore radius and a parallel shunt pathway of nonrestrictive pores characterized by a parameter, ω_o, that estimates the fraction of total filtrate passing through the shunt. We reported previously that type 2 diabetes (T2D) associated with an increase in ω_o. Here we examine whether ω_o associates with incident kidney failure or death in Pima Indians with T2D.

Methods

Iothalamate GFR and fractional clearance of dextrans of graded sizes were measured in 185 adults (74 men, 111 women) with T2D. ω_o was computed from the dextran sieving data. Hazard ratios (HR) for kidney failure or death were expressed per 1 standard deviation (SD) increase of ω_o by Cox regression after adjusting for age, sex, GFR, ACR, HbA1c and mean arterial blood pressure (MAP).

Results

At baseline, mean age (±SD) was 43±10 years, diabetes duration 8.8±8.7 years, HbA1c 8.9±2.4%, MAP 93±12 mm Hg, GFR 147±46 ml/min, and median (IQR) ACR was 41 (10-229) mg/g. During a median follow-up of 29 years, 70 participants developed kidney failure and 134 died, 60 after developing kidney failure. Baseline ω_owas higher in participants who developed kidney failure (0.00262 ± 0.00095 vs 0.00204 ±0.00077, P=0.0016) or died (0.00240 ± 0.00086 vs 0.00188 ± 0.00097, P=0.015). After adjustment, each 1 SD increase in baseline ω_o associated with increased risk of kidney failure (HR: 1.60, 95% CI 1.20-2.14) and death (HR: 1.34, 95% CI 1.06-1.68) [Table].

Conclusion

Enhanced transglomerular passage of test macromolecules associated with kidney failure and death, independent of albuminuria and GFR, suggesting that mechanisms responsible for impaired glomerular barrier size selectivity are important determinants of adverse health outcomes in T2D.

Hazard ratio for kidney failure and death according to baseline shunt coefficient (ωo)

*adjusted for age sex GFR ACR HbA1c and MAP

Funding

• NIDDK Support